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ENFERMEDAD METASTÁSICA
Carcinoma No Microcítico de Pulmón
Xabier Mielgo Rubio MDUnidad de Oncología
Hospital Universitario Fundación Alcorcón
CONTENIDO
1. CNMP CON MUTACIONES DRIVER– EGFR– ALK– ROS1– KRAS G12C– RET
2. CNMP SIN MUTACIONES DRIVER– QT y antiangiogénicos– Inmunoterapia
2L 1L
CNMP CONmutaciones
driver
EGFR
Soria et al. N Eng J Med 20187; Ramaligangam SS et al at ESMO, LBA5 PR
FLAURA OS ANALYSIS
38,6 vs 31,9m; HR 0,79, p=0,0462
EGFR
Soria et al, N Eng J Med 2018; Ramaligangam SS et al at ESMO, LBA5_PR
FLAURA OS ANALYSISConfirms role of osimertinibas SoC 1L in commonEGFRm NSCLC
Prolongs survival, with betterCNS activity and bettertolerability than 1st G TKIs
Careful! only 30% of control arm received osimertinib and 30% did not receive further tx
EGFRGef VS Gef + Chemo
Noronha V et al at ASCO, Abs 9001
EGFR
Zhang V et al at WCLC, OA11:07
Updated NCT02148380
•Only PS 0 or 1 patiens taken, unlike Indian study
•Brain Metastases included
•Uncommon mutations not included
•Chemo Schedule every 4 weekly
•Small numbers in each subgroup
EGFR
Zhang V et al at WCLC, OA11:07
Updated NCT02148380
AE, n (%)AC + G (n=40) G (n=41)Al Grade 3-4 All Grade 3-4
Liver dysfunction 21 (52.5) 4 (10.0) 15 (36.6) 1 (2.4)
Neutropenia 17 (42.5) 4 (10.0) 3 (7.3) 0 (0.0)Astriction 19 (47.5) 0 (0.0) 5 (12.2) 0 (0.0)Fatigue 9 (22.5) 3 (7.5) 7 (17.1) 0 (0.0)Anemia 17 (42.5) 0 (0.0) 11 (26.8) 0 (0.0)Nausea 20 (50.0) 0 (0.0) 6 (14.6) 0 (0.0)Diarrhea 19 (46.3) 0 (0.0) 17 (41.5) 0 (0.0)Skin rash 24 (60.0) 4 (10.0) 22 (53.7) 4 (9.8)Anorexia 16 (40.0) 0 (0.0) 8 (19.5) 0 (0.0)Thrombocytopenia 10 (25.0) 0 (0.0) 2 (4.9) 0 (0.0)
Leucopenia 8 (20.0) 0 (0.0) 3 (7.3) 0 (0.0)
Impressive 3 year OS data, however the numbers are small
Active in patients with CNS metastases (number of patients not mentioned)
No data available on T790M mutation and postprogression therapies
Better toxicity profile than other studies
3rd study with OS and PFS benefitStrategy Trial Treatment Median PFS,
monthsPFS HR (95%
CI)Median OS,
monthsOS HR (95%
CI)
1st
generation EGFR TKI + chemothera
py
NEJ009 Gefitinib + carbo-pemetrexed vs.
gefitinib
20.9 vs.11.2 months
0.49 (0.39-0.63)
52.2 vs.38.8 months
0.60 (0.52-0.93)
Noronha Gefitinib + carbo-pemetrexed vs.
gefitinib
16 vs. 8 months
0.51 (0.39-0.66)
NR vs. 17 months
0.45 (0.31-0.65)
Current study
Zhang Gefitinib + carbo-pemetrexed vs.
gefitinib vsPemetrexedCarboplatin
17.5 vs11.9 vs 5.7
months
0.48(0.29-.78) 37.9 vs 25.8 months
0.56(0.34-091)
EGFR
Nakagawa K et al at ASCO, Abs 9000
RELAY
EGFR
Nakagawa K et al at ASCO, Abs 9000
RELAY
Confirms benefit of the strategyof EGFR TKI + antiangiogenesis
Impressive PFS
More toxicity because of more hypertension
¿alternative to the SoCosimertinib?
EGFR
Zhou Q et al at ESMO, 14800
CTONG 1509
Confirms benefit in PFS of thestrategy of EGFR TKI + antiangiogenesis (RELAY, JO25567, NEJ026
No new safey signals
¿erlotinib + bevacizumab/ramucirumabalternative to the SoCosimertinib?
NO new safety signals
EGFR
Reck M et al at ELCC, 104O
IMpower 150 EGFR subgroup
N= 10% of ITT populationPossibly good alternative in EGFRm NSCLC afterprogression to TKIs
Small number of patients
Exploratory subanalysis
NCT03991403 phase III trial in EGFR and ALK population willclear the doubts
ALK
Chow L et al at ESMO, 14780
ASCEND-7 Arm Brainmets
ALK
Barlesi F et al at ESMO, 3900
ASCEND-7 Arm LM
ALK
Camidge D et al at ESMO, 1487PD
LORLATINIB post2nd G
ALK
Wolf J et al at WCLC, A02.07
ALUR updated Final Analysis
ALK
Gadgeel SM et al at ESMO, LBA81_PR
BFAST ALK cohort
ROS1
Barlesi et al at ELCC, Abs 1090
ENTRECTINIBIntegrated analysis
ROS1
Paz-Ares L et al at WCLC, MA14.02
ENTRECTINIBROS1/NTRK solid
tumors with CNS Mets
ROS1
Drilon A et al at ESMO, 444PD
REPROTECTINIBTRIDENT-1 Study
Phase I/II
KRAS G12C
Lanman BA et al at AACR, Abs 4455; Fakih M et al at ASCO, Abs 3003; Govindan R et al at ESMO, 446PD
AMG 510
RET
Drilon A et al at WCLC
LIBRETO-001(LOXO-292)
ORR 68% ORR 85%
RET
Gainor et al at ASCO,
ARROW(BLU-667)
CNMP SINmutaciones
driver
QT + ANTIANGIOGÉNICOS
Mantenimiento Pemetrexed + Bevacizumab
Seto T et al at ASCO, Abs 9003
Ramalingam SS et al at ASCO, Abs 9902
INMUNOTERAPIA 2L
Garon EB et al at ASCO, LBA9015
KeyNote-001 5-Y-OS
IO 2LActualizaciones
NIVOLUMAB
CheckMate-003: 6-Y-OS
CheckMate-017/057: 5-Y-OS
Gettinger S et al at WCLC, OA14.04Antonia SJ et al, Lancet Oncol 2019
IO 2L
Bazhenova L et al at WCLC, OA04.01
S1400I (Lung-MAP)
IO 2L
Arrieta O et al at WCLC, MA11.04
Pembro + Docetaxel
Pneumonitis grade 1-2: 22,5% vs 5,3%; p=0,029
INMUNOTERAPIA 1L
Spigel et al at ESMO, LBA78
Impower 110
IO 1L
Peters S et al at ESMO, LBA4_PR
CheckMate-227 Part 1 Final analysis
IO 1LCheckMate-227 Part 1
Final analysis
Peters S et al at ESMO, LBA4_PR
IO 1L
Peters S et al at ESMO, LBA4_PR
CheckMate-227 Part 1 Final analysis
IO 1L
Peters S et al at ESMO, LBA4_PR
CheckMate-227 Part 1 Final analysis
IO 1L
Borghaei et al at WCLC
Pembro PD-L1 < 1%
IO 1L
Mok T et al at ELCC, 102O
ActualizacionesPEMBROLIZUMAB
Reck M et al at WCLC
KeyNote-024 3-Y-OS
KeyNote-042 Final Analysis
IO 1L
Gadgeel SM et al at ASCO; Abs 9013
ActualizacionesPEMBROLIZUMABKeyNote-189: 18,7m follow
up and PFS2
IO 1LActualizacionesPEMBROLIZUMAB
KeyNote-407: Final analysis and PFS2
Paz-Ares L et al at ESMO, LBA82
TAKE-HOME MESSAGES
• Ratificación de osimertinib como SoC en EGFR+ mutaciones comunes (↑OS, ↑actividad intracraneal, ↓toxicidad)
• EGFR+ QT + Gefitinib: ↑OS llamativo pero ↑ toxicidad
• EGFR+ Erlotinib + beva/ramucirumab: ↑PFS alternativas 1L
• Nueva diana molecular accionable KRAS G12C con datos prometedores del AMG 510
• No demostrado ↑OS con doble mantenimiento beva/pemetrexed en nsNSCLC, monoterapia sigue siendo el estándar
• Ratificación de colas de largos supervivientes a 5ª con nivo y pembro– En PD-L1<1% 5-y-OS de 8,9% vs 2% frente a Docetaxel
• Atezolizumab ↑OS en TC3 o IC3WT: nueva opción terapéutica para altos expresores de PD-L1
• Nivo + Ipi: ↑OS frente a QT– Mayor beneficio: PD-L1 >=50% y <1%
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